The present invention concerns carbamic acid derivatives or their phamaceutically acceptable acid addition salts having anti-amnesic activity, methods for preparing them, intermediates for preparing them, and anti-dementia comprising the carbamic acid derivatives or their pharmaceutically acceptable acid addition salts as an active ingredient.
Recently, with elongation of average life, dementia diseases such as Alzheimer type senile dementia have arisen as a great problem in medical as well as social field.
Patients of dementia show symptom such as loss of intellectual ability, disturbance of memory, disturbance of abstract thinking, verbal aphasia, apraxia, disorientation and so on, and the disturbance of fundamental functions lies in that of formation of memory or expressing ability of hold memory.
However, up to now there have been hardly any medicament to cure it effectively and hence rapid development of remedy thereof has been longed.
Then, for compounds analogous to carbamic acid derivatives of the present invention, there have been known compounds of a general formula (10) ##STR2## wherein R.sup.5 denotes ethyl, propyl or butyl group and R.sup.6 denotes hydroxy, butoxy, pentoxy, hexyloxy or heptoxy group, which is described in Pharmazie, 44,25, (1989), those of general formulae (11) and (12) ##STR3## wherein R.sup.7 denotes methyl, ethyl, n-propyl, iso-propyl or t-butyl group and R.sup.8 denotes methyl group or chlorine atom, ##STR4## wherein R.sup.9 denotes methyl, ethyl, n-propyl, iso-propyl, n-butyl, t-butyl group, R.sup.10 denotes hydrogen atom or methyl group, and R.sup.11 denotes methyl group substituted at o-position, halogen atom substituted at each position of o-, m- or p-position, methoxy group substituted at p-position and acetyl group substituted at p-position, having local anesthesia function described in J. Med. Chem., 14, 710 (1971), those of a general formula (13) ##STR5## wherein R.sup.12 denotes a hydrogen atom, methyl group or chlorine atom and R.sup.13 denotes a chlorine atom or methyl group substituted at o-, m- or p-position, synthesized for a comparative compound in application research of agent of anti-arterial sclerosis described in J. Pharma. Sci., 59, 303 (1970), those of general formula (14) ##STR6## wherein R.sup.14 denotes methyl, ethyl, n-propyl, n-butyl or phenyl group, having inhibitory action against cholinesterase described in Egypt. J. Pharma. Sci., 26, 267 (1985), and so forth. However, it is unknown at all that these carbamic acid derivatives display anti-amnesia action, and further these are different from carbamic acid derivatives of the present invention in the structure thereof.
The object of the present invention lies in providing a medicament for improving disturbance of memory which is effective to symptoms of dementia and having high safety factor, in considering the present status of patients of dementia as mentioned above.